Dataset Information

Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders.

ABSTRACT: Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM processing and the second was to assess differences in the proteomic composition of CM during natural ovulatory cycles obtained from intrauterine insemination (IUI) cycles and in vitro fertilization (IVF) cycles with controlled ovarian hyperstimulation. Proteomic analysis of CM samples revealed 4370 proteins involved in processes including neutrophil degranulation, cellular stress responses, and hemostasis. Differential expression analysis revealed 199 proteins enriched in IUI samples and 422 enriched in IVF. The proteins enriched in IUI were involved in phosphatidic acid synthesis, responses to external stimulus, and neutrophil degranulation, while those enriched in IVF samples were linked to neutrophil degranulation, formation of a cornified envelope and hemostasis. Subsequent analyses clarified the protein composition of the CM and how it is altered by hormonal stimulation of the uterus.

SUBMITTER: Ozdian T

PROVIDER: S-EPMC9863546 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders.

Oždian Tomáš T Vodička Jan J Dostál Jiří J Holub Dušan D Václavková Jana J Ješeta Michal M Hamerníková Barbora B Kouřilová Pavla P Malchar Ondřej O Dvořák Vladimír V Hejtmánek Pavel P Sobková Kateřina K Ventruba Pavel P Pilka Radovan R Džubák Petr P Hajdúch Marián M

International journal of molecular sciences 20230105 2

Cervical mucus (CM) is a viscous fluid that is produced by the cervical glands and functions as a uterine cervix plug. Its viscosity decreases during ovulation, providing a window for non-invasive sampling. This study focuses on proteomic characterization of CM to evaluate its potential as a non-invasively acquired source of biomarkers and in understanding of molecular (patho)physiology of the female genital tract. The first objective of this work was to optimize experimental workflow for CM pro ...[more]

PMID: 36674559

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Project description:BackgroundEndometriosis is a chronic gynecological inflammatory disease characterized by the presence of functional endometrial glands and stroma outside of the uterine cavity. It affects 7-10% of women of reproductive age and up to 50% of women with infertility. The current gold standard for the diagnosis combines laparoscopic evaluation and biopsy of the visualized lesions. However, laparoscopy requires general anesthesia and developed surgical skills and it has a high procedural cost. In addition, it is associated with the risk, although rare, of potential intraoperative or postoperative complications. To date, several noninvasive biomarkers have been proposed; however, no definite diagnostic biomarker is yet available. The aim of this study was to characterize the CM proteome in patients with endometriosis using high resolution mass spectrometry-based proteomics, implemented by bioinformatic tools for quantitative analysis, in order to investigate the pathophysiological mechanisms of endometriosis.MethodsCervical mucus samples were collected from patients affected by endometriosis and fertile controls. An aliquot of the soluble acidic fraction of each cervical mucus sample, corresponding to 0.5 mg of total protein, was left to digest with sequencing grade modified porcine trypsin. The peptides were analyzed by LC-MS/MS on a high resolution Orbitrap Elite mass spectrometer and data were evaluated using bioinformatic tools.ResultsWe aimed at the first total profiling of the cervical mucus proteome in endometriosis. From the list of identified proteins, we detected a number of differentially expressed proteins, including some functionally significant proteins. Six proteins were quantitatively increased in endometriosis, almost all being involved in the inflammatory pattern. Nine proteins were quantitatively reduced in endometriosis, including some proteins related with local innate immunity (CRISP-3 and Pglyrp1) and protection against oxidative stress (HSPB1). Fifteen proteins were not detected in endometriosis samples including certain proteins involved in antimicrobial activity (SLURP1 and KLK13) and related to seminal plasma liquefaction and male fertility (KLK13).ConclusionsThis is the first application of high resolution mass spectrometry-based proteomics aimed in detecting an array of proteins in CM to be proposed for the noninvasive diagnosis of endometriosis. This chronic disease presents in CM an inflammatory protein pattern.

Project description:Vaginal microbicides hold great promise for the prevention of viral diseases like HIV, but the failure of several microbicide candidates in clinical trials has raised important questions regarding the parameters to be evaluated to determine in vivo efficacy in humans. Clinical trials of the candidate microbicides nonoxynol-9 (N9) and cellulose sulfate revealed an increase in HIV infection, vaginal inflammation, and recruitment of HIV susceptible lymphocytes, highlighting the need to identify biomarkers that can accurately predict microbicide toxicity early in preclinical development and in human trials. We used quantitative proteomics and RT-PCR approaches in mice and rabbits to identify protein changes in vaginal fluid and tissue in response to treatment with N9 or benzalkonium chloride (BZK). We compared changes generated with N9 and BZK treatment to the changes generated in response to tenofovir gel, a candidate microbicide that holds promise as a safe and effective microbicide. Both compounds down regulated mucin 5 subtype B, and peptidoglycan recognition protein 1 in vaginal tissue; however, mucosal brush samples also showed upregulation of plasma proteins fibrinogen, plasminogen, apolipoprotein A-1, and apolipoprotein C-1, which may be a response to the erosive nature of N9 and BZK. Additional proteins down-regulated in vaginal tissue by N9 or BZK treatment include CD166 antigen, olfactomedin-4, and anterior gradient protein 2 homolog. We also observed increases in the expression of C-C chemokines CCL3, CCL5, and CCL7 in response to treatment. There was concordance in expression level changes for several of these proteins using both the mouse and rabbit models. Using a human vaginal epithelial cell line, the expression of mucin 5 subtype B and olfactomedin-4 were down-regulated in response to N9, suggesting these markers could apply to humans. These data identifies new proteins that after further validation could become part of a panel of biomarkers to effectively evaluate microbicide toxicity.

Dataset Information

Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders.

Publications

Proteome Mapping of Cervical Mucus and Its Potential as a Source of Biomarkers in Female Tract Disorders.

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